Gradient and spin echo (GRASE) is a pulse sequence that makes images with high signal sampling rates for medical magnetic resonance imaging (MRI). Long echo trains maintain relatively high signal amplitude due to the presence of several 180° RF refocusing pulses that cause signal decay by T2 in spin echoes and by stimulated echo magnetization pathways. The number of refocused echoes in GRASE can easily exceed 500 echoes and, with so many signals obtained from one RF excitation pulse, they can be used to obtain high spatial resolution in single-shot 2D images. A single-shot image is an image made from a single echo train and from a single excitation RF pulse. The long echo trains of GRASE can also be used to make single-shot 3D images by means of additional phase encoding pulses on a second gradient axis. The bandwidth of the phase encoding gradient axes depends on the time interval between sampled points in k-space. With the RF spin echo refocusing between each 2D k-space sampling, the time sampling on the second phase encoded axis is constant and has no evolution of phase errors and therefore no bandwidth related variations in phase error due to Bo inhomogeneity, susceptibility and other off-resonance phase errors that may be present and constant in the data acquisition. The phase encoded image axis of the EPI gradient refocused signals does have bandwidth dependent phase errors, identical to a 2D EPI echo train sequence. Therefore the image distortions and signal loss in regions of high susceptibility are artifacts present in 3D GRASE images.
The phase errors in the 3D GRASE images can be reduced by sampling data at a higher bandwidth, and smaller echo time interval within the gradient refocused echo train between the RF pulses. With the shorter time evolution of phase errors, the artifacts and distortions are reduced; however, this improvement is only up to a point determined by increasing the frequency of gradient switching. The physiologic stimulation of peripheral nerve activity is a biological limitation of gradient switching and increasing the frequency of gradient refocusing of signals. Therefore, on a current generation MRI scanner from Siemens used by at least one of the named inventors, a minimum of 600 microseconds time interval between echoes is typical limit before physiologic stimulations occur or are a consideration. Even at this rapid echo refocusing, there are considerable distortions in regions of the brain near the frontal sinus containing air with high susceptibility, and signal loss occurs there and in the lower temporal lobes due to bone-brain interfaces of susceptibility phase errors in signals.
We have discovered that the combination of segmented 3D GRASE with arterial spin labeling (ASL) has unexpected and great advantages over other 3D ASL techniques including spiral, EPI, TSE and RARE. We have discovered that the physiological variations in cardiac pulsations in cerebrospinal fluid (CSF) and of arterial blood flow do not introduce artifacts into the segmented 3D GRASE sequence. We have also discovered that the blood oxygen level dependent (BOLD) changes can introduce significant variability in signal changes into Spiral and EPI ASL sequences, which can degrade accurate calculation of blood flow in ASL because the T2* encoding is greater in these sequences. However, the GRASE ASL has negligible BOLD encoding because it has spin echo refocusing that nearly eliminates BOLD contamination in the signal. We further discovered that the signal loss in brain regions from susceptibility artifacts is reduced in half or greater in GRASE compared to spiral and EPI. We have discovered that the unique combination of three processes 1) ASL 2) 3D GRASE and 3) multiple segments, when combined together, create the highest speed and quality in blood perfusion images and give an ability to control and reduce the susceptibility artifacts, reduce the T2 dependent blurring and obtain images with fewer signal averages than EPI or TSE segmented sequences and thus obtain higher spatial resolution of blood perfusion in reduced scan times.
Segmented imaging with TSE or RARE is generally slow and inefficient. At present, in our experience ASL using segmented 3D TSE sequences requires 16 minutes to scan while similar spatial resolution in 3D GRASE images requires only 30 seconds using the new combination of segmented data to reduce distortions, blurring, and raise signal-to-noise ratio (SNR). To our knowledge, segmented 3D GRASE has been utilized prior to this work for anatomical images but not for blood flow image and it encountered problems and image artifacts due to movement of CSF which had different velocity dependent phase errors due to different cardiac phase timing in different segments encoded in different excitation cycles of the sequence. These motion dependent amplitude and phase variations in vessels and CSF create severe ghost artifacts which obscure the true image and make it poorly interpretable. The Spiral sequence has specific advantage in eliminating these phase errors, as is well known from its use in cardiac imaging and from functional MRI. Spiral encodes the central region of k-space, where the greatest signal energy occurs in k-space, utilizing the beginning of the Gr gradient oscillation where there is no gradient or minimal gradient amplitude and it is the product of spin velocity and gradient amplitude which contributes to the velocity dependent phase errors, therefore with minimal gradients utilized there is negligible velocity phase error. Therefore, Spiral ASL sequences have shown minimal ghosting artifacts, however, unlike GRASE where the center of k-space and maximum signal occurs after several repeated Gr gradient pulses which accumulate velocity phase errors. But we have discovered that in ASL GRASE, the initial 180° blood labeling pulse stores all signals in the longitudinal plane, so the blood and CSF signal is stored on the longitudinal axis and does not accumulate any phase errors. Also, the background tissue suppression pulses utilized in ASL sequences only reduce signal from stationary tissues and from the CSF, but it doesn't remove these phase errors. The use of an inversion pulse to label blood prior to the readout GRASE sequence allows blood to enter the volume of tissue, regardless of the pulsatility effects, and so the volume of blood within a voxel of tissue is not affected by arterial variations in blood flow. Both the CSF and stationary brain tissue signals are subtracted to zero, nulled, by subtracting a non labeled from a blood labeled image in ASL. We have discovered that this combination of ASL and GRASE allows the use of segmented data either acquired within the same excitation echo train, or from multiple echo trains each acquired with separate excitation pulses, essentially without degradation due to pulsatility artifacts and ghosts from velocity phase shifts. Normally the EPI gradient echoes in GRASE are the source of velocity dependent phase shifts that differ in different phases of the cardiac cycle, each differently effecting the different excitations, so that there can be large discontinuities in phase errors in the final combined k-space data set. In contrast, the combination of ASL with the background suppression and 3D GRASE provides images that can be made with a large number of gradient echo signals to reduce the scan time and raise SNR. This reduction of scan time is not present in segmented EPI or segmented TSE sequences because these sequences are much less efficient and cannot obtain a large number of signals in each segmented data set.
Previously, we and other scientists have combined single echo trains of 3D GRASE with ASL because the segmented 3D GRASE anatomical images without using ASL had artifacts from blood motion and CSF motion which are encoded with different phase errors on different excitations. For this reason, the ability to successfully combine multiple segments of k-space from separately excited echo trains in ASL 3D GRASE appeared to have no practical value due to well known artifacts, and to our knowledge has not been used for imaging.
The advantages of ASL 3D GRASE over 2D EPI is more signals, reduced distortions, reduced artifacts, higher SNR, and less scan time.
Compared to 3D Spiral ASL imaging, the invention 3D ASL GRASE has higher SNR, and does not have the severe susceptibility artifacts of signal loss in Spiral because GRASE centers that k-space on spin echoes where there is no susceptibility artifact, unlike Spiral imaging which places the echoes forming the center of k-space on one side of the gradient signal encoding waveform which is on a gradient echo time so there is T2* and susceptibility error that causes large susceptibility signal drop-out and image artifacts.
3D Spiral RARE ASL (also called 3D Spiral TSE ASL) has efficiency advantages similar to segmented 3D GRASE ASL, however, it places the beginning of the spiral which is the center of k-space, onto a gradient echo position at the beginning or end of each time interval between the RF refocusing pulses. This causes susceptibility artifacts in the image associated with the spiral positioning, and it also creates a nonlinear signal change due to T2* BOLD contrast mechanisms which cannot be separated from the ASL signal, preventing accurate quantitative measurements of CBF. The 3D spiral TSE ASL has T2* BOLD signal changes because the ko data has much higher signal than outer regions of k-space and the ko is at the beginning of the spiral where there is T2* contrast, unlike 3D GRASE ASL in which the ko is positioned at the center of the RF pulse interval, on a SE which has T2, not T2* contrast mechanisms. The key to success of 3D GRASE has been its high SNR, low artifact load due to the CPMG timing, and whole brain coverage made possible with the simplified physiological timing in 3D acquisitions.
Compared to 3D EPI, the new invention provides more signals for higher SNR and reduced scan time, and much less distortion and blurring. It is important to note that when two single-shot sequences are interleaved, as in segmented 3D acquisitions, this would reduce artifacts from differences in velocity dependent phase shifts with the two echo trains occurring at different points in the cardiac cycle with different CSF and blood velocities.
Compared to 3D TSE, the new invention provides much more signal, higher SNR, greatly reduced scan time, with similar distortions and blurring and similar artifacts from susceptibility. The efficiency of obtaining a large number of signals in each 3D GRASE echo train reduces the scan time significantly. ASL images have very little signal due to the fraction of blood being a small percent in the tissue, typically 3 to 5% with signal reduced proportionally. The larger number of signals in 3D GRASE raises the image SNR and therefore reduces the number of redundantly encoded signal that are averaged to obtain sufficient SNR to make a resolvable image. Compared to 3D TSE or 3D EPI sequences, the GRASE sequence provides more signals per unit time.
The new approach includes interleaving two or more echo trains from different segmented excitations or from adjacent RF periods in k-space, resulting in half the accumulated phase errors in k-space. Phase errors are reduced in echo trains by reducing RF pulse spacing. Interleaving of the signals from two or more shorter segments of echoes centered on spin echoes in separate RF excitation periods or in refocused periods within a single echo train, are interleaved in k-space to give 3D data sets.